My goals in seeking a K23 award are to investigate the pathophysiology of atherosclerosis in patients with HIV infection and to develop a career in clinical research. My specific research interests are determining the roles of inflammation and immunity in the pathogenesis of atherosclerotic disease in patients with HIV infection for the purpose of improving treatment of cardiovascular disease and developing new therapies in this patient population. In order to accomplish this, I have assembled a strong mentoring committee with researchers with expertise in clinical research, HIV disease, and cardiovascular imaging. I plan to obtain training in clinical research methodologies and to perform a series of mentored research projects that will give me the training I need to become an independent clinical researcher. The use of antiretroviral therapy has decreased HIV-related morbidity and mortality; however, cardiovascular disease is becoming an important new health issue for HIV-infected patients, which will likely continue to increase in incidence in the future. The pathophysiology behind this process remains unclear. I am interested in investigating the roles of inflammation and altered immunity in the development of atherosclerosis in treated HIV patients. I propose the following specific aims:
(Aim 1) To assess the role of inflammation in atherosclerosis and plaque formation and atherosclerotic progression in HIV-infected patients as compared to HIV-negative control subjects;
(Aim 2) To assess the relationship between T cell activation and atherosclerosis and atherosclerotic progression in HIV-infected patients;
(Aim 3) To conduct a randomized trial to assess the short-term effects of statin therapy on markers of inflammation and T cell activation in HIV-infected individuals, and to provide preliminary estimates of effect of size and variance of carotid IMT and coronary calcification in this population. We hypothesize that baseline measurements of inflammation and T cell activation will be higher in HIV-infected patients and will be associated with higher baseline levels of atherosclerosis and atherosclerotic progression over time. In addition, we hypothesize that intervention with statin therapy will decrease markers of inflammation and T cell activation.
For Aims 1 and 2, I plan to recruit patients from an established cohort study.
For Aim 3, I will conduct a pilot randomized trial in which I will design and implement a small independent clinical research project.
